基于生理学的毒动力学模型,对小鼠中的三二乙烯酸盐 (TCEP) 进行了对多种暴露途径的计算
Jiaqi Ding1, Wanyu He1, Wanxiao Sha1
1Key laboratory of Pollution process and Environmental Criteria of Ministry of Education and Tianjin Key Laboratory of Environmental Technology for Complex Trans-Media Pollution, College of Environmental Science and Engineering, Nankai University, Tianjin 300071, China.
基于生理学的毒性动力学 (PBTK) 模型预测化学度 in vivo. 这项研究开发了一种PBTK模型,用于小鼠和人类的三二乙烯酸盐 (TCEP),评估来自不同暴露途径的风险.
科学领域:
- 环境毒理学环境毒理学
- 计算毒理学计算毒理学
- 风险评估 风险评估 风险评估
背景情况:
- 暴露途径显著影响化学品对健康风险的评估.
- 基于生理学的毒动力学 (PBTK) 模型提供了具有成本效益的体内预测.
- 有机酸 (OPE) 和酸 (TCEP) 等有机酸 (OPE) 是常见的环境污染物.
研究的目的:
- 开发和验证PBTK模型用于TCEP在小鼠考虑多个暴露路径 (口腔和皮肤).
- 建立基于小鼠模型的TCEP人类PBTK模型.
- 对全球暴露于TCEP的人口进行健康风险评估.
主要方法:
- 建立了小鼠TCEP的多部位PBTK模型,包括血液,肝脏,脏,胃,肠,皮肤和身体其他部位.
- 用实验数据验证了小鼠PBTK模型,在5倍偏差范围内达到>70%的预测准确度.
- 推断出验证的小鼠模型来开发人类PBTK模型进行风险评估.
主要成果:
- 不同的暴露途径 (口腔与皮肤) 导致小鼠的TCEP分布模式不同.
- 口服TCEP暴露主要集中在胃肠道和肝脏.
- 皮肤TCEP暴露导致皮肤,身体其他部位和血液中的度更高.
- 在暴露后30分钟内,TCEP在小鼠中呈现出快速的吸收和积累.
- 人类PBTK模型表明,摄入 (食物) 的TCEP风险高于皮肤接触.
- 风险评估显示,通过尘埃摄入TCEP比通过皮肤与尘埃接触的风险更大.
- 与灰尘相比,中国人面临的TCEP风险更高.
结论:
- 开发的PBTK模型准确地预测了TCEP动力学和组织积累在不同的暴露路径.
- 这项研究为各种人群的TCEP健康风险提供了宝贵的见解.
- PBTK建模是化学风险评估和跨物种推断的强大工具.
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